Ingestion and killing of bacteria by polymorphonuclear neutrophils is an important part of the normal host defense against bacterial infection. The principal investigator plans to continue studies concerning normal mechanisms as well as studies on derangement of PMN bactericidal activity. Certain virulent bacteria resist killing by PMN. To understand the factors involved, we plan to study the relationship of microbial catalase (which destroys hydrogen peroxide) and superoxide dismutase (which destroys superoxide) with in vitro and in vivo virulence. This should help to clarify the role of products of oxidative metabolism in the bactericidal activity of leukoyctes. We also plan to investigate the influence of enterotoxins on the interaction of E. coli with polymorphonuclear neutrophils. The enterotoxins have been shown to stimulate adenylate cyclase of mammalian cells and this effect could have profound influences on PMN function. Since anaerobic PMN are able to kill certain bacteria, some microorganisms must be killed by non-oxidative means. The role of lactoferrin, acid, lysozyme, cationic proteins, and other components of the bactericidal activity will be investigated. Gonococci have the ability to stick to many surfaces including external membrane of the PMN. The effect of membrane adherence versus ingestion will be studied. This, we should clarify the role of various types of bacterial-PMN interaction on stimulation of periphagocytic events such as oxygen consumption, hexose monophosphate shunt activity, degranulation, and bactericidal activity. BIBLIOGRAPHIC REFERENCES: Minor MR, Sande MA, Dilworth JA and Mandell GL: Cefamandole Treatment of Pulmonary Infection Due to Gram Negative Rods. J Antimicrob Chemother 2:49-53, 1976. Verklin RM and Mandell GL: Alteration of Effectiveness of Antibiotics by Anaerobiosis. J Lab and Clin Med:88-65, 1977.